Long-term survival of participants in the CENTAUR trial of sodium phenylbutyrate-taurursodiol in amyotrophic lateral sclerosis

Authors

• Sabrina Paganoni, Harvard Medical School
• Suzanne Hendrix, Pentara Corporation
• Samuel P. Dickson, Pentara Corporation
• Newman Knowlton, Pentara Corporation
• Eric A. Macklin, Harvard Medical School
• James D. Berry, Harvard Medical School
• Michael A. Elliott, Swedish Medical Center, Seattle
• Samuel Maiser, Departments of Neurology
• Chafic Karam, Oregon Health & Science University
• James B. Caress, Wake Forest School of Medicine
• Margaret Ayo Owegi, UMass Memorial Medical Center
• Adam Quick, The Ohio State University College of Medicine
• James Wymer, University of Florida College of Medicine
• Stephen A. Goutman, University of Michigan, Ann Arbor
• Daragh Heitzman, Texas Neurology
• Terry D. Heiman-Patterson, Lewis Katz School of Medicine
• Carlayne E. Jackson, University of Texas Health Science Center at San Antonio
• Colin Quinn, University of Pennsylvania Perelman School of Medicine
• Jeffrey D. Rothstein, Johns Hopkins University
• Edward J. Kasarskis, University of Kentucky College of Medicine
• Jonathan Katz, California Pacific Medical Center
• Liberty Jenkins, California Pacific Medical Center
• Shafeeq Ladha, Barrow Neurological InstituteFollow
• Timothy M. Miller, Washington University School of Medicine in St. Louis
• Stephen N. Scelsa, Icahn School of Medicine at Mount Sinai
• Tuan H. Vu, Morsani College of Medicine
• Christina N. Fournier, Emory University School of Medicine
• Jonathan D. Glass, Emory University School of Medicine
• Kristin M. Johnson, Ochsner Health System
• Andrea Swenson, University of Iowa Carver College of Medicine
• Namita A. Goyal, UCI School of Medicine

Document Type

Article

Abstract

© 2020 The Authors. Muscle & Nerve published by Wiley Periodicals LLC. An orally administered, fixed-dose coformulation of sodium phenylbutyrate-taurursodiol (PB-TURSO) significantly slowed functional decline in a randomized, placebo-controlled, phase 2 trial in ALS (CENTAUR). Herein we report results of a long-term survival analysis of participants in CENTAUR. In CENTAUR, adults with ALS were randomized 2:1 to PB-TURSO or placebo. Participants completing the 6-month (24-week) randomized phase were eligible to receive PB-TURSO in the open-label extension. An all-cause mortality analysis (35-month maximum follow-up post-randomization) incorporated all randomized participants. Participants and site investigators were blinded to treatment assignments through the duration of follow-up of this analysis. Vital status was obtained for 135 of 137 participants originally randomized in CENTAUR. Median overall survival was 25.0 months among participants originally randomized to PB-TURSO and 18.5 months among those originally randomized to placebo (hazard ratio, 0.56; 95% confidence interval, 0.34-0.92; P =.023). Initiation of PB-TURSO treatment at baseline resulted in a 6.5-month longer median survival as compared with placebo. Combined with results from CENTAUR, these results suggest that PB-TURSO has both functional and survival benefits in ALS.

Publication Date

1-1-2021

Publication Title

Muscle and Nerve

ISSN

0148639X

E-ISSN

10974598

Volume

63

Issue

1

First Page

31

Last Page

39

PubMed ID

33063909

Digital Object Identifier (DOI)

10.1002/mus.27091

Recommended Citation

Paganoni, Sabrina; Hendrix, Suzanne; Dickson, Samuel P.; Knowlton, Newman; Macklin, Eric A.; Berry, James D.; Elliott, Michael A.; Maiser, Samuel; Karam, Chafic; Caress, James B.; Owegi, Margaret Ayo; Quick, Adam; Wymer, James; Goutman, Stephen A.; Heitzman, Daragh; Heiman-Patterson, Terry D.; Jackson, Carlayne E.; Quinn, Colin; Rothstein, Jeffrey D.; Kasarskis, Edward J.; Katz, Jonathan; Jenkins, Liberty; Ladha, Shafeeq; Miller, Timothy M.; Scelsa, Stephen N.; Vu, Tuan H.; Fournier, Christina N.; Glass, Jonathan D.; Johnson, Kristin M.; Swenson, Andrea; and Goyal, Namita A., "Long-term survival of participants in the CENTAUR trial of sodium phenylbutyrate-taurursodiol in amyotrophic lateral sclerosis" (2021). Neurology. 576.
https://scholar.barrowneuro.org/neurology/576